Cognitive Decline

Whole-cell perforated recording from RGCs or tectal cells were made under visual control by methods described previously 28 . The micropipettes were made from borosilicate glass capillaries (Kimax), had a resistance in the range of 2-3 MQ, and were tip-filled with internal solution and then were back-filled with internal solution containing 200 mg ml 21 amphotericin B. The internal solution contained: 115 mM K-gluconate, 4 mM NaCl, 1.5 mM MgCl 2 , 20 mM HEPES at pH 7.3 and 0.5 mM EGTA. Recordings were made with a patch clamp amplifier (Axopatch 200A; Axon Instruments). The whole cell capacitance was fully compensated and the series resistance (10-20 MQ) was compensated at 75-80% (lag 60 ms) and monitored during the experiment. The data were discarded if the series resistance varied by .20%. The input resistance of RGCs at 260 to 270 mV was usually in the range of 0.5 to 1 GQ. Signals were filtered at 5 kHz and sampled at 10 kHz using Axoscope software (Axon Instruments). For cell-attached recording, the pipette was filled with bath solution and a loose seal was made. To record mEPSCs from RGCs or tectal neurons, TTX (1 mM) was added to external solution. A total amount of 400 ng BDNF (PeproTech), dissolved in 15 ml bath solution containing 0.1% bovine serum albumin (BSA), was puffed into the third ventricle near the tectum through a Picospritzer II (General Valve), using a micropipette with a tip opening of 6 mm and repetitive pressure pulses (5 psi, 0.5 Hz, 1 s duration). It usually took 15 min for the BDNF-containing solution to be completely ejected. A small LCD-screen (Sony, PLM-A35) was mounted on the camera port of the microscope, allowing projection of computer-generated images onto the retina of the tadpole. Light responses were evoked by whole-field stimulations with a step (4 s) increase in the whole-field light illumination. All drugs were from Sigma.

Dopaminergic treatments are associated with impulse control disorders such as pathological gambling in a subset of patients with Parkinson's Disease. While deep brain stimulation of the subthalamic nucleus has been reported to reduce symptoms of impulse control disorders in some Parkinson's Disease patients, little is known about its specific effects on gambling behaviour. In this experiment, we investigated the effects of deep brain stimulation of the subthalamic nucleus on one of the central features of pathological gambling: the tendency to chase losses. Loss-chasing is associated with impaired control over gambling behaviour and it is one of the most salient features of pathological gambling as it presents in the clinic. Twenty two patients with advanced idiopathic Parkinson's Disease and chronically implanted subthalamic nucleus electrodes for deep brain stimulation completed a simple laboratory model of loss-chasing behaviour twice: once with and once without stimulation. Exploratory analysis indicated that deep brain stimulation of the subthalamic nucleus increased the value of losses chased by patients with Parkinson's Disease when shifting from off- to on-stimulation. These effects were not attributable to changes in state affect or to the motor impairments produced by the withdrawal of deep brain stimulation of the subthalamic nucleus. The effects of the stimulation on the value of losses chased were more pronounced in female than in male patients and reduced in patients taking dopamine receptor agonists. Collectively, these results suggest that deep brain stimulation of the subthalamic nucleus can transiently alter the evaluation of accumulated losses during gambling episodes in idiopathic Parkinson's Disease.► We study the effects of STN DBS on gambling behaviour in Parkinson's Disease (PD). ► STN DBS transiently increases the value of losses chased by PD patients. ► These effects are less pronounced in male patients and under dopamine agonists.

Normal aging is associated with cognitive decline. Functions such as attention, information processing, and working memory are compromised. It has been hypothesized that not only regional changes, but also alterations in the integration of regional brain activity (functional brain connectivity) underlie the observed agerelated deficits. Here, we examined the functional properties of brain networks based on spontaneous fluctuations within brain systems using functional magnetic resonance imaging. We hypothesized that functional connectivity of intrinsic brain activity in the ''default-mode'' network (DMN) is affected by normal aging and that this relates to cognitive function. Ten younger and 22 older subjects were scanned at ''rest,'' that is, lying awake with eyes closed. Our results show decreased activity in older versus younger subjects in 2 resting-state networks (RSNs) resembling the previously described DMN, containing the superior and middle frontal gyrus, posterior cingulate, middle temporal gyrus, and the superior parietal region. These results remain significant after correction for RSN-specific gray matter volume. The relevance of these findings is illustrated by the correlation between reduced activity of one of these RSNs and less effective executive functioning/processing speed in the older group.

The IQCODE is widely used as a screening test for dementia, particularly where the subject is unable to undergo direct cognitive testing or for screening in populations with low levels of education and literacy. This review draws together research on the psychometric properties and validity of the IQCODE.

Deciphering the secret of successful aging depends on understanding the patterns and biological underpinnings of cognitive and behavioral changes throughout adulthood. That task is inseparable from comprehending the workings of the brain, the physical substrate of behavior. In this review, we summarize the extant literature on age-related differences and changes in brain structure, including postmortem and noninvasive magnetic resonance imaging (MRI) studies. Among the latter, we survey the evidence from volumetry, diffusion-tensor imaging, and evaluations of white matter hyperintensities (WMH). Further, we review the attempts to elucidate the mechanisms of age-related structural changes by measuring metabolic markers of aging through magnetic resonance spectroscopy (MRS). We discuss the putative links between the pattern of brain aging and the pattern of cognitive decline and stability. We then present examples of activities and conditions (hypertension, hormone deficiency, aerobic fitness) that may influence the course of normal aging in a positive or negative fashion. Lastly, we speculate on several proposed mechanisms of differential brain aging, including neurotransmitter systems, stress and corticosteroids, microvascular changes, calcium homeostasis, and demyelination. r

Critical requirements for the hypothesis that executive functioning is a potential mediator of age-related effects on cognitive functioning are that variables assumed to reflect executive functioning represent a distinct construct and that age-related effects on other types of cognitive functioning are reduced when measures of executive functioning are statistically controlled. These issues were investigated in a study involving 261 adults between 18 and 84 years of age. Although age-related effects on various cognitive abilities were substantially reduced after statistical control of the variance in measures hypothesized to represent executive functioning, there was only weak evidence for the existence of distinct constructs corresponding to executive functioning or to aspects of executive control concerned with inhibition, updating, or time sharing.

Cholinergic neuron loss is a cardinal feature of Alzheimer disease. Nerve growth factor (NGF) stimulates cholinergic function, improves memory and prevents cholinergic degeneration in animal models of injury, amyloid overexpression and aging. We performed a phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain. After mean follow-up of 22 months in six subjects, no long-term adverse effects of NGF occurred. Evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested improvement in the rate of cognitive decline. Serial PET scans showed significant (P < 0.05) increases in cortical 18-fluorodeoxyglucose after treatment. Brain autopsy from one subject suggested robust growth responses to NGF. Additional clinical trials of NGF for Alzheimer disease are warranted.

We have reviewed the published data regarding radiotherapy (RT)-induced brain injury. Radiation necrosis appears a median of 1-2 years after RT; however, cognitive decline develops over many years. The incidence and severity is dose and volume dependent and can also be increased by chemotherapy, age, diabetes, and spatial factors. For fractionated RT with a fraction size of <2.5 Gy, an incidence of radiation necrosis of 5% and 10% is predicted to occur at a biologically effective dose of 120 Gy (range, 100-140) and 150 Gy (range, 140-170), respectively. For twice-daily fractionation, a steep increase in toxicity appears to occur when the biologically effective dose is >80 Gy. For large fraction sizes ($2.5 Gy), the incidence and severity of toxicity is unpredictable. For single fraction radiosurgery, a clear correlation has been demonstrated between the target size and the risk of adverse events. Substantial variation among different centers' reported outcomes have prevented us from making toxicity-risk predictions. Cognitive dysfunction in children is largely seen for whole brain doses of $18 Gy. No substantial evidence has shown that RT induces irreversible cognitive decline in adults within 4 years of RT. Ó 2010 Elsevier Inc.

A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population.

Background: Several studies have suggested that physical activity is positively associated with cognitive function in elderly persons. Evidence about this association has been limited by the cross-sectional design of most studies and by the frequent lack of adjustment for potential confounding variables. We determined whether physical activity is associated with cognitive decline in a prospective study of older women.

. Finally, when younger adults perform multiple tasks simultaneously (e.g., divided attention), frontal activity is attenuated and task performance becomes impaired paralleling that observed in older adults under full attention conditions Prior imaging studies have suggested that older St. Louis, Missouri 63110 adults often fail to recruit specific frontal regions during 5 Howard Hughes Medical Institute memory encoding to the same extent as younger adults, St. Louis, Missouri 63110 in particular during intentional encoding where effective encoding strategies must be spontaneously initiated (e.g., Anderson, et al., 2000; Cabeza et al., 1997; Grady Summary et al., 1995, 1999; Madden et al., 1999b; for review, see Grady and Craik, 2000)

We present a series of 26 patients, all 150 years of age, who are carriers of the fragile X premutation and are affected by a multisystem, progressive neurological disorder. The two main clinical features of this new syndrome are cerebellar ataxia and/or intention tremor, which were chosen as clinical inclusion criteria for this series. Other documented symptoms were short-term memory loss, executive function deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower limb proximal muscle weakness, and autonomic dysfunction. Symmetrical regions of increased T2 signal intensity in the middle cerebellar peduncles and adjacent cerebellar white matter are thought to be highly sensitive for this neurologic condition, and their presence is the radiological inclusion criterion for this series. Molecular findings include elevated mRNA and low-normal or mildly decreased levels of fragile X mental retardation 1 protein. The clinical presentation of these patients, coupled with a specific lesion visible on magnetic resonance imaging and with neuropathological findings, affords a more complete delineation of this fragile X premutation-associated tremor/ataxia syndrome and distinguishes it from other movement disorders.

This meta-analysis of 28 data sets (N ¼ 705 older adults, N ¼ 962 younger adults) examined age differences in emotion recognition across four modalities: faces, voices, bodies/contexts, and matching of faces to voices. The results indicate that older adults have increased difficulty recognising at least some of the basic emotions (anger, sadness, fear, disgust, surprise, happiness) in each modality, with some emotions (anger and sadness) and some modalities (face-voice matching) creating particular difficulties. The predominant pattern across all emotions and modalities was of age-related decline with the exception that there was a trend for older adults to be better than young adults at recognising disgusted facial expressions. These age-related changes are examined in the context of three theoretical perspectives-positivity effects, general cognitive decline, and more specific neuropsychological change in the social brain. We argue that the pattern of age-related change observed is most consistent with a neuropsychological model of adult aging stemming from changes in frontal and temporal volume, and/or changes in neurotransmitters. r

Cerebral small-vessel disease is common in older people and may contribute to the development of dementia. The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospective, population-based Rotterdam Scan Study. Participants were 60-90 years of age and free from dementia at baseline in 1995-1996. White matter lesions (WML), cerebral infarcts and generalized brain atrophy were assessed on the baseline MRI. We performed neuropsychological testing at baseline and repeatedly in 1999-2000 and in 2001-2003. We used random-effects models for repeated measures to examine the association between quantitative MRI measures and rate of decline in measures of global cognitive function, information processing speed, executive function and memory. There were a total of 2266 assessments for the 832 participants in the study, with an average time from the initial to last assessment of 5.2 years. Increasing severity of periventricular WML and generalized brain atrophy and the presence of brain infarcts on MRI were associated with a steeper decline in cognitive function. These structural brain changes were specifically associated with decline in information processing speed and executive function. The associations between MRI measures of cerebral small-vessel disease and cognitive decline did not change after additional adjustment for vascular risk factors or depressed mood. After exclusion of participants with an incident stroke, some of the associations of periventricular WML, brain infarcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant. This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline. Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function.

White matter microstructural integrity was assessed using diffusion tensor imaging (DTI) in 25 young adults, 25 nondemented older adults, and 25 age-matched older adults with dementia of the Alzheimer type (DAT). For each individual, measures of anisotropy and diffusivity were obtained from atlas-transformed images in the anterior and posterior callosum and in the frontal, parietal, temporal and occipital white matter. These data revealed age differences in anisotropy and diffusivity in all assessed regions. Age effects were greater in the anterior as opposed to the posterior corpus callosum and greater in the frontal white matter than in the temporal, parietal and occipital white matter, suggesting age-associated differences in white matter that exhibit a roughly anterior-to-posterior gradient. In contrast, individuals with early-stage dementia exhibited minimal, if any, additional change in anterior regions but did show greater deterioration of white matter in posterior lobar regions. Taken collectively, these results indicate that nondemented aging is characterized by significant changes in white matter most prominently in anterior brain regions. The dissociation between the regional effects of age and dementia status suggests that the mechanisms underlying age-associated cognitive decline are likely distinct from those underlying DAT.

Cognitive function, with survival and response on brain imaging, is increasingly regarded as an important outcome measure in patients with brain tumours. This measure provides us with information on a patient&#39;s clinical situation and adverse treatment effects. Radiotherapy has been regarded as the main cause of cognitive decline in these patients, because children with brain tumours can develop intellectual deterioration caused by radiotherapy. In long-term surviving patients, radiotherapy may indeed lead to cognitive deficits, or even dementia. Recent studies, however, have made clear that focal radiotherapy in patients with glioma is not the main reason for cognitive deficits. The tumour itself and other medical treatments contribute largely to the cognitive deficits. Cognitive function is now also recognised as an independent prognostic factor in the survival of glioma patients. Additionally, cognitive deterioration can be the first indicator of progressive disease after trea...

An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B(6) and B(12) in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B(12) (0.5 mg/d) and vitamin B(6) (20 mg/d), the other with ...

Alzheimer's disease. Moreover, the pattern of cerebral blood flow in mild cognitive impairment has emerged as a predictive marker for the progression into Alzheimer's disease. The reconstruction of a pathological condition in animal models is a suitable approach to the unraveling of causal relationships. For this reason, permanent, bilateral occlusion of the common carotid arteries (2VO) in rats has been established as a procedure to investigate the effects of chronic cerebral hypoperfusion on cognitive dysfunction and neurodegenerative processes. Over the years, the 2VO model has generated a large amount of data, revealing the 2VO-related pattern of cerebral hypoperfusion and metabolic changes, learning and memory disturbances, failure of neuronal signaling, and the neuropathological changes in the hippocampus. In addition, the model has been introduced in research into ischemic white matter injury and ischemic eye disease. The present survey sets out to provide a comprehensive summary of the achievements made with the 2VO model, and a critical evaluation and integration of the various results, and to relate the experimental data to human diseases. The data that have accumulated from use of the 2VO model in the rat permit an understanding of the causative role played by cerebral hypoperfusion in neurodegenerative diseases. Thorough characterization of the model suggests that 2VO in the rat is suitable for the development of potentially neuroprotective strategies in neurodegenerative diseases.

The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer's disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants.

Background. Previous studies have reported an 11% to 75% incidence of postoperative cognitive decline among cardiac surgery patients. The INVOS Cerebral Oximeter (Somanetics Corp, Troy, MI) is a Food and Drug Administration approved device that measures regional cerebral oxygen (rSO 2 ) saturation. The purpose of this study is to examine whether decreased rSO 2 predicts cognitive decline and prolonged hospital stay after coronary artery bypass grafting (CABG).

The present review integrates findings of published studies that have evaluated the cognitive function of treated and untreated type 2 diabetic patients and provides a detailed overview of the neuropsychological assessments conducted. Cognitive deficits are observed in older people with glucose intolerance or untreated diabetes but these deficits appear to be attenuated by treatments that improve glycemic control. Cognitive decrements in treated type 2 diabetic patients are most consistently observed on measures of verbal memory (35% of the measures) and processing speed (45% of the measures) while preserved function is observed on measures of visuospatial, attention, semantic and language function. Some studies suggest that deficits in cognitive functions are associated with poorer glycemic control. A number of other factors, such as depression, cardiovascular and cerebrovascular disease, increase these deficits. We conclude that, in diabetic patients who achieve and maintain good glycemic control, type 2 diabetes only has a small impact on cognitive functions before the age of 70 years. However, early onset of type 2 diabetes, poor glycemic control and the presence of micro-and macrovascular disease may interact to produce early cognitive deficits. In older adults (70 years and over), diabetes likely interacts with other dementing processes such as vascular disease and Alzheimer's disease to hasten cognitive decline.

This review aims to address issues unique to older adults with anxiety disorders in order to inform potential changes in the DSM-V. Prevalence and symptom expression of anxiety disorders in late life, as well as risk factors, comorbidity, cognitive decline, age of onset, and treatment efficacy for older adults are reviewed. Overall, the current literature suggests: (a) anxiety disorders are common among older age individuals, but less common than in younger adults; (b) overlap exists between anxiety symptoms of younger and older adults, although there are some differences as well as limitations to the assessment of symptoms among older adults; (c) anxiety disorders are highly comorbid with depression in older adults; (d) anxiety disorders are highly comorbid with a number of medical illnesses; (e) associations between cognitive decline and anxiety have been observed; (f) late age of onset is infrequent; and (g) both pharmacotherapy and CBT have demonstrated efficacy for older adults with anxiety. The implications of these findings are discussed and recommendations for the DSM-V are provided, including extending the text section on age-specific features of anxiety disorders in late life and providing information about the complexities of diagnosing anxiety disorders in older adults. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.

Background: Homozygotes for the thermolabile mutation (TT genotype) of the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) enzyme have elevated plasma concentrations of the cardiovascular disease risk factor homocysteine, particularly if folate depleted. Objective: We examined the relations between thermolabile MTHFR, plasma homocysteine, plasma folate, and vascular disease risk. Design: This was a case-control comparison in 711 vascular disease cases and 747 controls from 9 European countries. Results: The TT genotype was associated with higher homocysteine and lower plasma folate than the CC and CT genotypes in both cases and controls and a nonsignificant increase in vascular disease risk (1.26; 95% CI: 0.88, 1.81; P = 0.20). The frequency of the TT genotype in cases was not significantly different from that in controls (12.8% compared with 10.8%). After adjustment for traditional risk factors, the TT genotype was associated with an odds ratio of 1.48 (1.0, 2.20) for risk of vascular disease. This risk was attenuated after further adjustment for homocysteine. In subgroups with homocysteine concentrations ≥ 9 mol/L, risk tended to be higher in CC than in TT subjects. However, CC subjects were characterized by a higher prevalence of the conventional risk factors associated with both elevated plasma homocysteine and serum creatinine. After adjustment, the risk of vascular disease associated with each genotype was not significantly different. Conclusions: There was a strong graded association between homocysteine and vascular risk in all genotypes. MTHFR genotype is a key determinant of plasma total homocysteine concentrations. The initially nonsignificant risk estimate associated with the TT genotype was strengthened after adjustment for conventional cardiovascular disease risk factors but was attenuated after adjustment for plasma folate and total homocysteine. The modest risk increase conferred by the TT genotype is mediated mainly by increased total homocysteine and low plasma folate concentrations.

A novel MRI method-diVusion tensor imaging-was used to compare the integrity of several white matter fibre tracts in patients with probable Alzheimer's disease. Relative to normal controls, patients with probable Alzheimer's disease showed a highly significant reduction in the integrity of the association white matter fibre tracts, such as the splenium of the corpus callosum, superior longitudinal fasciculus, and cingulum. By contrast, pyramidal tract integrity seemed unchanged. This novel finding is consistent with the clinical presentation of probable Alzheimer's disease, in which global cognitive decline is a more prominent feature than motor disturbance. (J Neurol Neurosurg Psychiatry 2000;69:528-530)

Brain aging is associated with a progressive imbalance between antioxidant defenses and intracellular concentrations of reactive oxygen species (ROS) as exemplified by increases in products of lipid peroxidation, protein oxidation, and DNA oxidation. Oxidative conditions cause not only structural damage but also changes in the set points of redoxsensitive signaling processes including the insulin receptor signaling pathway. In the absence of insulin, the otherwise low insulin receptor signaling is strongly enhanced by oxidative conditions. Autophagic proteolysis and sirtuin activity, in turn, are downregulated by the insulin signaling pathway, and impaired autophagic activity has been associated with neurodegeneration. In genetic studies, impairment of insulin receptor signaling causes spectacular lifespan extension in nematodes, fruit flies, and mice. The predicted effects of age-related oxidative stress on sirtuins and autophagic activity and the corresponding effects of antioxidants remain to be tested experimentally. However, several correlates of aging have been shown to be ameliorated by antioxidants. Oxidative damage to mitochondrial DNA and the electron transport chain, perturbations in brain iron and calcium homeostasis, and changes in plasma cysteine homeostasis may altogether represent causes and consequences of increased oxidative stress. Aging and cognitive decline thus appear to involve changes at multiple nodes within a complex regulatory network.

In light of the rising prevalence of Alzheimer&#39;s disease (AD), new strategies to prevent, halt, and reverse this condition are needed urgently. Perturbations of brain network activity are observed in AD patients and in conditions that increase the risk of developing AD, suggesting that aberrant network activity might contribute to AD-related cognitive decline. Human amyloid precursor protein (hAPP) transgenic mice simulate key aspects of AD, including pathologically elevated levels of amyloid-β peptides in brain, aberrant neural network activity, remodeling of hippocampal circuits, synaptic deficits, and behavioral abnormalities. Whether these alterations are linked in a causal chain remains unknown. To explore whether hAPP/amyloid-β-induced aberrant network activity contributes to synaptic and cognitive deficits, we treated hAPP mice with different antiepileptic drugs. Among the drugs tested, only levetiracetam (LEV) effectively reduced abnormal spike activity detected by elect...

To determine the effectiveness of community based occupational therapy on daily functioning of patients with dementia and the sense of competence of their care givers. Design Single blind randomised controlled trial. Assessors were blinded for treatment allocation. Setting Memory clinic and day clinic of a geriatrics department and participants' homes. Participants 135 patients aged ≥ 65 with mild to moderate dementia living in the community and their primary care givers.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year re-search project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer's disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of

Atherosclerosis and thrombosis may lead to cognitive Impairment through cerebral infarcts or white matter hyperintensities. Oxidative stress is now seen as a major contributor to the process of atherogenesis. High intake of polyunsaturated fatty acids, e.g., linoleic acid, or low intake of antioxidants can increase oxidative stress. High intake of n-3 polyunsaturated fatty acids and its main source, fish, may reduce the risk of thrombosis. Little is known, however, about the relation between these dietary factors and cognitive function. The authors investigated this relation with data derived from a cohort of men, aged 69-89 years, who were participants in the Zutphen Elderly Study. The 30-point Mini-Mental State Examination was used to assess cognitive impairment in 1990 (score s25 in 153/476 men, 32%) and cognitive decline from 1990 to 1993 (drop >2 points in 51/342 men, 15%). Food intake was estimated in 1985 and 1990 by the cross-check dietary history method. High linoleic acid intake was associated with cognitive impairment after adjustment for age, education, cigarette smoking, alcohol consumption, and energy intake (odds ratio (OR) for highest vs. lowest fertile = 1.76, 95% confidence interval (Cl) 1.04-3.01). Intake of n-3 polyunsaturated fatty acids was not associated with cognitive impairment, whereas high fish consumption tended to be inversely associated with cognitive impairment (OR = 0.63, 95% Cl 0.33-1.21) and cognitive decline (OR = 0.45, 95% Cl 0.17-1.16). Intakes of beta-carotene, vitamins C and E, and flavonoids were not inversely associated with cognitive impairment or decline. This study raises the possibility that high linoleic acid intake is positively associated with cognitive impairment and high fish consumption inversely associated with cognitive impairment. Am J Cognitive performance decreases with increasing age. Cognitive impairment is a major component of dementia and influences the individual's ability to function independently. Due to aging of the population, the prevalence of cognitive impairment is expected to increase. Therefore, it is important to elucidate possible modifiable risk factors for impaired cognitive function, such as diet.

In the current article, we provide a critical review of the extant literature that has focused on environmental influences on cognitive and brain plasticity over the adult life span. The review includes both human epidemiological, and human and nonhuman cross-sectional and longitudinal research. We review a number of factors that have been suggested to reduce age-related cognitive decline including both formal and informal education, leisure pursuits, intellectual engagement, and expertise in different skill domains. We also examine the literature on cognitive and physical fitness training. We conclude with a discussion of the gaps in the literature and suggestions for future research.